Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

• Minimum time to a requirement for involved-field radiotherapy (IFRT), requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause [ Designated as safety issue: No ]
• Minimum time to a relapse of higher risk at any time, any relapse following treatment with protocol-mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm [ Designated as safety issue: No ]
• Minimum time to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving more than one drug (combination chemotherapy) and giving them together with radiation therapy may kill more cancer cells.

PURPOSE: This phase III trial is studying how well combination chemotherapy works when given before radiation therapy and/or additional chemotherapy in treating young patients with newly diagnosed Hodgkin's lymphoma.

OBJECTIVES:

• Investigate the paradigm of response-based therapy for low-risk Hodgkin's lymphoma by eliminating involved-field radiotherapy (IFRT) in patients who achieve a complete remission (CR) after initial chemotherapy.
• Investigate whether 3 courses of doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide (AV-PC) for the treatment of low-risk Hodgkin's lymphoma is sufficient to induce CR in at least 80% of patients.
• Investigate whether patients who experience a low-risk relapse after initial treatment with chemotherapy alone can be successfully treated with a salvage regimen comprising ifosfamide and vinorelbine ditartrate with dexamethasone, etoposide phosphate, cisplatin, and cytarabine (IV/DECA) and IFRT. (Salvage therapy closed as of 1/17/2012)
• Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above 97%.
• Determine the prognostic significance of very early response as measured by fludeoxyglucose-positron emission tomography (FDG-PET) or gallium after the first course of chemotherapy.
• Evaluate the prognostic significance of elevation of erythrocyte sedimentation rate and C-reactive protein at the time of diagnosis in patients with low-risk Hodgkin's lymphoma on CR rate and relapse rate after chemotherapy alone.
• Determine the frequency and severity of late effects of therapy, including thyroid dysfunction, infertility, cardiotoxicity, and second malignant neoplasms.

OUTLINE: This is a multicenter study.

• Initial chemotherapy: Patients receive doxorubicin hydrochloride IV over 10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and 8, oral prednisone on days 1-7, and filgrastim (G-CSF) subcutaneously (SC) on days 3-7 and 9-14. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) proceed to observation. Patients achieving partial remission proceed to radiotherapy. Patients who have a low-risk relapse after achieving CR on initial chemotherapy proceed to salvage chemotherapy followed by radiotherapy. Patients who have stable disease or disease progression go off study.
• Salvage chemotherapy: Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1-5, and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then receive dexamethasone IV over 15 minutes every 12 hours, etoposide phosphate IV over 3 hours every 12 hours, and cytarabine IV over 3 hours every 12 hours on days 1 and 2; cisplatin IV over 6 hours on day 1; and G-CSF SC or IV beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then proceed to radiotherapy. (Salvage therapy closed as of 1/17/2012)
• Involved-field radiotherapy (IFRT): Beginning 4 weeks after completion of chemotherapy, patients undergo IFRT once daily, 5 days a week, for 2.8 weeks. Patients who do not achieve CR go off study.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate
• Radiation: selective external radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma meeting the following criteria:

  • Newly diagnosed disease

  • Stage IA OR stage IIA without bulky disease

    • Bulky disease is defined as a large mediastinal mass or large extramediastinal nodal aggregate
  • No lymphocyte-predominant histology

PATIENT CHARACTERISTICS:

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
• Bilirubin ≤ 1.5 times normal
• ALT ≤ 2.5 times normal
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA
• No pathologic prolongation of QTc interval on 12-lead ECG
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy
• At least 30 days since prior systemic corticosteroids
• No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
• No concurrent corticosteroid therapy